Seady, Marina

Abstract Description The importance of microglia class I restricted antigen presentation to brain-infiltrating CD8 T cells has been difficult to define. To address this question, our laboratory generated novel single MHC Class I conditional knockout mice in which H-2Kb or H-2Db can be deactivated specifically in Tmem119+ microglia with tamoxifen administration. Recombinant Theiler’s murine encephalomyelitis virus (TMEV) encoding the model antigen OVA enabled analysis of virus antigen-specific CD8 T cells restricted to Kb class I molecules while Daniel’s strain TMEV Db class I molecules enabled analysis of Db:VP2 specific CD8 T cells. Our results revealed profound differences between MHC class I molecules. Conditional knockout of Kb in Tmem119+ microglia reduced Kb:OVA epitope specific CD8 T cells in the brain compared to Cre negative littermate controls. Employing methodology using FTY720 and BrdU labeling, we determined that deletion of Kb in Tmem119+ microglia reduced proliferation and numbers of Kb:OVA specific CD8 T cells in the brain compared to Cre negative littermate controls. Meanwhile, mice with deletion of Db in Tmem119+ microglia had reduced levels of perforin in Db:VP2 CD8 T cells. These findings demonstrate there are discrete roles for specific MHC Class I molecules on microglia during CNS viral infection. These results plus transgenic mouse systems will help further our understanding of brain infiltrating CD8 T cell responses in neurologic disease. Funding Sources Supported by R01NS122174 and R01NS103212 Topic Categories Neuroimmunology (NEUR)